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A3189
October 15, 2018
10/15/2018 3:30:00 PM - 10/15/2018 5:30:00 PM
Room North, Hall D, Area A
Phase 2 Study of Fibrinogen Concentrate Vs Cryoprecipitate in Pseudomyxoma Peritonei Surgery: Interim Results
Ashok Roy, M.D., Nigel Sargant, M.D., Savita Rangarajan, M.D., Sue Alves, M.D., John Bell, M.D., Sophia Stanford, M.D., Cristina Solomon, M.D., MBA, Irina Kruzhkova, M.D., Sigurd Knaub, M.D., Faheez Mohamed, M.D.
Basingstoke and North Hampshire Hospital, Basingstoke, United Kingdom
Disclosures: A. Roy: None. N. Sargant: None. S. Rangarajan: None. S. Alves: None. J. Bell: None. S. Stanford: None. C. Solomon: Salary; Self; Octapharma AG. I. Kruzhkova: Salary; Self; Octapharma AG. S. Knaub: Salary; Self; Octapharma AG. F. Mohamed: None.
Background: Pseudomyxoma peritonei (PMP) is a rare entity that usually results from a perforated primary appendiceal tumor. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (the Sugarbaker procedure) is the established optimal treatment. Acquired fibrinogen deficiency and clinically-relevant bleeding are common complications of this procedure. Maintaining adequate plasma fibrinogen concentration during surgery may help control hemostasis. We present interim results from FORMA-05, a study comparing the hemostatic efficacy and safety of two sources of fibrinogen: a new highly purified, double virus-inactivated human fibrinogen concentrate (Fibryga/Octafibrin; Octapharma) and cryoprecipitate.

Methods: FORMA-05 is a prospective, single center, randomized, controlled phase 2 study in patients with acquired fibrinogen deficiency undergoing cytoreductive surgery for PMP. The study aims to enroll up to 55 patients. Individuals who required intraoperative fibrinogen supplementation (predicted intraoperative blood loss ≥2 L without fibrinogen supplementation) were randomized to receive Fibryga (4 g) or cryoprecipitate (2 pools, 5 units each) preemptively. Further doses of Fibryga or cryoprecipitate up to 24 h postoperatively were to be administered if the A20 parameter of the thromboelastometry FIBTEM test decreased to ≤12 mm. The primary endpoint was a composite of intraoperative efficacy (assessed by the surgeon and anesthesiologist at the end of surgery) and postoperative efficacy (assessed by the hematologist 24 h after the end of surgery), graded using an objective four-point scale and adjudicated by an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC).

Results: This planned interim analysis included 23 patients in the per-protocol set, 10 that received Fibryga and 13 that received cryoprecipitate. During the 7.7 ± 1.4 h of surgery, 6.4 ± 2.8 g of Fibryga (85 ± 36 mg/kg bw) and 3.9 ± 1.7 pools of 5 units of cryoprecipitate were used, respectively. 100% of patients in both groups, with 95% CIs of 69.2–100% for the Fibryga group and 75.3–100% for the cryoprecipitate group, were adjudicated as having achieved ‘treatment success’. Intraoperative hemostatic efficacy, as assessed by the surgeon and anesthesiologist, was judged to be ‘excellent’ or ‘good’ for 90.0% of the patients that received Fibryga and 76.9% of those that received cryoprecipitate (IDMEAC: 90.0% vs. 61.5%). Postoperative hemostatic efficacy was deemed by the hematologist and IDMEAC to be ‘excellent’ for all 23 patients. Overall, intraoperative Fibryga administration led to mean increases of 0.7 g/L in plasma fibrinogen concentration and 3.1 mm in FIBTEM A20 (p<0.0001 for both), while intraoperative cryoprecipitate administration led to mean increases of 0.3 g/L (p=0.0023) and 0.6 mm (p=0.5501), respectively. Significantly higher increases in fibrinogen concentration were obtained with Fibryga than with cryoprecipitate (p=0.0127).

Intraoperative blood loss did not differ significantly between groups, with 1,291 mL (SD ±319) and 1,429 mL (SD ±486) for the Fibryga and cryoprecipitate groups, respectively (p=0.446). Only a median of 1 unit of red blood cells was administered intraoperatively, with 0 units administered during the first 24 hours postoperatively in each group. No transfusion of fresh frozen plasma or platelet concentrates was given. The occurrence of adverse events (AEs) appeared comparable between the two groups, with 29 in 10/11 patients (90.9%) in the Fibryga group and 44 in 12/13 patients (92.3%) in the cryoprecipitate group, including 2 serious AEs in the Fibryga group and 9 in the cryoprecipitate group, none assessed as related to study drug administration.

Conclusions: In this interim analysis, Fibryga was efficacious and had a favorable safety profile in the treatment of bleeding related to acquired fibrinogen deficiency in patients undergoing cytoreductive surgery for PMP.

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